Research Article Use of Flattening Filter-Free …downloads.hindawi.com/archive/2014/769698.pdfResearch Article Use of Flattening Filter-Free Photon Beams in Treating Medulloblastoma:

Research ArticleUse of Flattening Filter-Free Photon Beams inTreating Medulloblastoma: A Dosimetric Evaluation

Pichandi Anchineyan,1 Ganesh K. Mani,2 Jerrin Amalraj,1

Balaji Karthik,1 and Surega Anbumani1

1 CyberKnife Center, HealthCare Global Enterprises, No. 7, HCG Tower 2, Kalinga Rao Road, Sampangiram Nagar,Bangalore 560 027, India

2Department of Radiation Physics, Kidwai Memorial Institute of Oncology, Bangalore 560029, India

Correspondence should be addressed to Pichandi Anchineyan; [email protected]

Received 30 September 2013; Accepted 4 November 2013; Published 21 January 2014

Academic Editors: R.-J. Bensadoun and L.-M. Sun

Copyright © 2014 Pichandi Anchineyan et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Aim. To evaluate the dosimetric benefits of flattening filter-free (FFF) photon beams in intensity modulated radiation therapy(IMRT) and Rapid Arc (RA) over conventional CSI methods.Methods and Materials. Five patients treated with IMRT using staticmultileaf collimators (MLC) were randomly selected for this retrospective study. DynamicMLC IMRT, RA, and conformal therapy(3DCRT) were iterated with the same CT data sets with and without flattening filter photons. Total dose prescribed was 28.80Gyin 16 fractions. Dosimetric parameters such as 𝐷max, 𝐷min, 𝐷mean, 𝑉95%, 𝑉107%, DHI, and CI for PTV and 𝐷max, 𝐷mean, 𝑉80%, 𝑉50%,𝑉30%, and 𝑉10% for OARs were extracted from DVHs. Beam on time (BOT) for various plans was also compared. Results. FFF RA

therapy (6F RA) resulted in highly homogeneous and conformal doses throughout the craniospinal axis. 3DCRT resulted in thehighest𝑉

107% (SD) 46.97±28.6, whereas flattening filter (FF) and FFF dynamic IMRT had aminimum𝑉107%. 6F RA and 6F DMLC

resulted in lesser doses to thyroid, eyes, esophagus, liver, lungs, and kidneys. Conclusion. FFF IMRT and FFF RA for CSI havedefinite dosimetric advantages over 3DCRT technique in terms of target coverage and OAR sparing. Use of FFF in IMRT resultedin 50% reduction in BOT, thereby increasing the treatment efficiency.

1. Introduction

Medulloblastoma is a fast growing tumor of the cerebellum(posterior fossa) that controls stability, posture, and complexmotor functions such as verbal communication and swallow-ing.

About 400 new patients, primarily children, were diag-nosed in the US every year, slightly more often in malesthan in females [1]. It is the most common brain tumorin children aged four and younger and the second mostcommon brain tumor in children aged 5–14 years [2].Subsequent to surgery, medulloblastoma is usually treatedwith CSI. Although radiation therapy had proven successful,investigators are still looking for new ways to mitigate thepotential side effects of this treatment [2]. Treatment relatedlate complications are usually hearing disability, declined cog-nition, cardiomyopathy, cataract formation, retarded growth,

endocrine dysfunction, and second malignancies. Cliniciansconsider using techniques such as IMRT and RA that aimto converge beams of radiation directly at the tumor even-tually improving the long term complications free survival.However, radiotherapy (RT) planning, delivery, and junctiondose verification remain exigent for craniospinal irradiation(CSI) in medulloblastoma patients. Hence investigating theemerging new RT techniques such as FFF in IMRT and RAon the basis of dose volume parameters was encouraged toreduce the normal tissue complications [3].

Conventional two-dimensional planning forCSI involvedfield shaping using bony landmarks in X-ray radiographs;later it evolved into CT simulation techniques [4, 5]. Geomet-rical fieldmatchingwas generally followed in such techniqueswithout computing any dose volume data for the tumor andnormal tissues. Modified treatment planning methods wereadapted to get better tumor coverage, dose homogeneity,

Hindawi Publishing CorporationISRN OncologyVolume 2014, Article ID 769698, 5 pageshttp://dx.doi.org/10.1155/2014/769698

2 ISRN Oncology

and conformity. The practicability of conventional linearaccelerator (LA) IMRT for CSI in small children had beenreported by Parker et al. [6]. The matching of cranial andspinal fields still poses a problem in adult patients with largerspinal lengths since it usually exceeds allowable maximumfield size. Helical tomotherapy allows treatment to largecylindrical volumes (40 × 160 cm2) that was compromisedwith the longer BOT. It raises concerns about intrafractionmotion and whole-body integral doses. When the FF wasremoved from the linear accelerators head, amarked increasein dose rate up to 1400MU/min for 6MV and 2400MU/minfor 10MV beams is possible.The higher dose rate couldmaketreatment delivery more accurate, by giving the patient lesstime to move between setup and treatment completion. Thismight be particularly helpful in CSI, where the tissues are farmore mobile than in the cranium.

There is no dosimetric comparison between flattenedand unflattened photon beams for CSI. The aim of thisstudy is to determine the feasibility of using FFF beamsin IMRT and RA for CSI in medulloblastoma patientsand to dosimetrically compare it with 3DCRT, IMRT withstatic segments (6X SMLC), IMRT with dynamic segments(6X DMLC), Rapid Arc therapy (6X RA) with FFF IMRT(6F DMLC), and Rapid Arc therapy (6F RA).

2. Methods and Materials

Patients were CT scanned from the vertex to coccyx inprone position using immobilization device (Orfit Industriesn.v., Belgium) on multislice CT scanner (GE Healthcare,USA). Axial images of 3mm slice thickness were exported toMimvista contouring station (MIM software Inc, USA)wherethe target volumes (PTV Brain, PTV Spine) and normalstructures were delineated by radiation oncologists as per therecommended guidelines [7]. PTV Spine included the entirespinal canal, including cerebrospinal extension to spinalganglia. OARs such as eyes, thyroid, heart, lungs, esophagus,liver, and kidney were outlined in the axial CT sections.Treatment planning was performed in Eclipse (Version 11.0;Varian Associates, Palo Alto, CA, USA) treatment planningsystem (TPS). It is configured for both true beammillennium120 multileaf collimator (MLC) and Siemens ARTISTE 160MLC treatment units. The range of patients’ spine lengthvaried from 28.52 cm to 43.75 cm (median length: 33.4 cm).A maximum field size of 40 × 40 cm2 can be possible withthe 120 millennium MLC and 160 MLC Artiste. Anisotropicanalytical algorithm was the dose calculation algorithm usedfor inverse optimization. We used the CT data set of fiverandomly selected medulloblastoma patients (median age:10 yrs), previously treated with conventional IMRT for thisretrospective study. Conventional 3DCRT plan, 6X DMLC,6F DMLC, 6X RA, and 6F RA were iterated which resultedin six plans for each patient. The total dose prescribedwas 28.80Gy in 16 fractions with 1.8 Gy per fraction. Anevaluation criterion of 98% of the PTV receiving 100% ofthe prescription dose and 107%maximum dose was followedas per our institution protocol. Normal tissue sparing wasconsidered as important as the tumor coverage.

3DCRT IMRT RA

Figure 1: Beam arrangements for 3DCRT, IMRT, and RA.

2.1. Radiotherapy with Conformal Photon Beams (3DCRT).The 3DCRT for CSI comprised three separate treatmentplans such as 3d Brain, 3d Spine1, and 3d Spine2. For thewhole brain irradiation, 6MV photon beam was collimatedin such a way that the spine field’s divergence can be easilymatched. Spine 1 comprised the region between 2nd cervicalvertebra, 10th thoracic vertebra and whereas spine 2 wasbetween 11th thoracic vertebra and 5th lumbar vertebra.Spinal cord treatments were planned with two oblique beamportals 330∘ and 30∘. The 25∘ enhanced dynamic wedgeswere used to avoid high-dose regions falling beneath theskin and to improve dose coverage at larger depths. For thethree plans, depth from skin where the maximum possiblecoverage achieved was taken as the reference point for dosenormalization. Plans were summed up in evaluation mode ofthe TPS to analyze the junction dose. The sagittal view of the3DCRT beam arrangement is shown in Figure 1.

2.2. Intensity Modulated RadiationTherapy (IMRT) Planning.IMRT confines the radiation dose more precisely to targetalone. This is achieved by modulating or controlling theradiation beam intensity in multiple beamlets. It also allowshigher radiation doses to be focused on regions within thetumor while minimizing the dose to surrounding OARs.IMRT delivery methods using conventional MLCs can berealized in several ways: (1) “step-and-shoot” static IMRTusingmultipleMLC shapes and (2) dynamic IMRTwith fixedgantry and moving MLC leaves. For CSI, jagged junction orintensity feathering technique was used to plan IMRT andRA plans. In this technique, 6MV photon beams with sameoptimization can be iterated (PTV) with multiple isocenters.Thus, summing up of two or three plans was not needed.The junction evaluation can be avoided which could be atedious process involving suitable collimator angles to matchdose gradients from the adjacent field. Since there was nobeam matching involved, this treatment technique is lesslikely to produce hot or cold spots at the junction, comparedto conventional techniques. Except for one tallest patient, allother cases were planned with two isocenters and 8 gantryangles. For the tallest of the patients, entire spine was splitinto three regions and two separate isocenters apart from thecranial junction were planned with 12 beam portals. Figure 1shows IMRTbeamarrangement. Beamgeometry consisted of

ISRN Oncology 3

Table 1: Dosimetric parameters for combined target volumes (brain and spine).

Combined target volumes (brain and spine)

Dosimetric parameters 3DCRT 6X SMLC 6X DMLC 6F DMLC 6X RA 6F RAMean SD Mean SD Mean SD Mean SD Mean SD Mean SD

𝐷max 34.31 0.81 32.91 0.67 31.97 0.91 31.87 0.41 32.26 0.61 32.62 0.63𝐷min 5.76 1.45 20.49 1.82 19.77 2.63 19.35 3.24 21.54 2.61 22.61 1.80𝐷mean 30.78 0.68 30.09 0.14 30.11 0.11 30.15 0.11 30.77 0.43 30.82 0.80𝐷2% 32.38 0.68 31.34 0.23 30.75 0.10 30.78 0.18 31.42 0.52 31.68 0.83𝐷98% 28.51 0.46 28.80 0.00 28.80 0.00 28.80 0.00 28.79 0.02 28.53 0.57𝑉95% 99.12 0.27 99.62 0.13 99.76 0.09 99.77 0.12 99.83 0.10 99.55 0.62𝑉107% 46.97 28.60 10.94 4.90 1.23 0.70 2.88 3.74 49.15 30.84 66.36 21.59

DHI 13.45 2.33 8.81 0.80 6.78 0.36 6.89 0.62 9.12 1.78 10.92 1.74CI 1.19 0.08 1.10 0.03 1.09 0.03 1.10 0.04 1.04 0.02 1.05 0.01

four coplanar fields for the whole skull with the gantry angles225∘, 115∘, 310∘, and 50∘ and upper spine with gantry angles20∘, 50∘, 340∘, and 310∘. In case of an additional isocenterfor the tallest of all patients, lower spine gantry angles are0∘, 30∘, and 60∘. Default smoothing values were used duringoptimization. To improve the results, efforts were made tomodify constraints and priority factors in IMRT plans.

2.3. Rapid Arc Therapy (RA). RA optimization was per-formed with version 11.0 from Eclipse (Varian, Palo Alto,CA, USA). The maximum dose rate (DR) of 600MU/minfor 6X RA and DR of 1600MU/Min for 6F RapidArc wasselected. All plans were done with 2 isocenters and 2 fullArcs (179∘–181∘) for each isocenter (Figure 1). These twoArcs were delivered in opposite rotations (clockwise andcounterclockwise). Collimator was set to rotate to a valueother than zero in order to avoid tongue and groove effect.The anisotropic analytical algorithm (AAA, version 11.00)was the dose calculation algorithm used.

2.4. Dose-Volume Analysis. Target coverage was quantifiedwith the conformity index (CI) based on International Com-mission of Radiation Units report: 50 (ICRU 50). The dosehomogeneity index (DHI) was calculated using the formulacoined by Wu et al. [8]. The dosimetric parameters suchas 𝐷max, 𝐷mean, 𝑉2%, 𝑉98%, 𝑉95%, and 𝑉107% were evaluatedfor the six planning techniques. The volumes of each OARreceiving >80% (high; 𝑉

80%), >50% (intermediate; 𝑉50%),

>30% (low; 𝑉30%), and >10% (low; 𝑉

10%) of the prescribeddose were extracted from the DVH and compared among thetechniques. The techniques were evaluated for average totalBOT.

3. Results

The sagittal dose distribution resulted from 3DCRT, IMRT,and RA techniques was shown in Figure 2. Among the sixtechniques, 3DCRT resulted inmaximumdose heterogeneity.6X DMLC and 6F RA lead to more homogeneous and con-formal doses throughout the craniospinal axis. Plan dosimet-ric parameters related to target coverage, homogeneity, and

Figure 2: Dose distribution from 3DCRT, IMRT, and RA tech-niques, sagittal view.

conformity resulting from the six techniques were presentedin Table 1.𝐷max,𝐷mean, 𝑉2%, 𝑉98%, and 𝑉95% values obtained in each

method were almost similar. 3DCRT had lesser minimumdose to target 𝐷min compared to other methods. It resultedin the highest 𝑉

107% (SD) 46.97 ± 28.6, whereas FF and FFFdynamic IMRT had a minimum 𝑉

107%. Dose statistics formaximummean dose (𝐷mean) for OARs were listed (Table 2).

There was no significant difference between OAR dosesresulted from 6X DMLC, 6F DMLC, 6X RA, and 6F RAplan exceptmeandose to lungs and eyes.Themean lungs dosefrom6X SMLCwas lesser (4.78±0.73Gy) than 6F RA (5.93±0.72Gy) and 6X RA (6.01 ± 72Gy). The mean dose to eyeswas 14.88Gy (6F RA) and 7.87Gy (3DCRT). The percentagevolumes of each OAR receiving 𝑉

80% and 𝑉50% of radiation

from the three different treatment planning techniques werepresented in Figures 3 and 4, respectively.

IMRT (FF/FFF) and RA (FF/FFF) reduction reduces theamount of OAR volume receiving doses such as 80%, 50%,and 30%. Mean dose, 𝑉

80%, 𝑉50%, and 𝑉30% for thyroid,heart, esophagus, lungs, liver, and kidneys were similar in allthe techniques except 3DCRT. Very low thyroid doses were

4 ISRN Oncology

Table 2: Mean dose data for OARs.

OAR𝐷mean in Gy

Dosimetric parameters 3DCRT 6X SMLC 6X DMLC 6F DMLC 6X RA 6F RAMean SD Mean SD Mean SD Mean SD Mean SD Mean SD

Rt eye 10.95 11.68 10.31 3.32 10.58 3.31 9.99 3.56 14.64 0.84 14.88 2.39Lt eye 7.87 3.93 11.65 2.57 11.73 2.61 11.35 2.79 14.43 1.07 14.91 2.64Thyroid 15.28 3.9 7.36 3.16 8.68 2.53 8.56 2.99 4.71 0.44 5.10 1.07Heart 7.24 2.15 2.81 0.77 3.08 0.77 4.09 3.01 3.62 0.58 3.56 0.66Esophagus 17.16 5.88 8.34 2.01 8.06 1.94 8.62 1.91 7.63 1.13 7.25 1.27Rt lung 4.98 0.73 4.78 0.73 4.85 0.84 4.63 0.85 6.01 0.72 5.93 0.72Lt lung 4.87 1.37 4.76 1.69 5.05 1.91 4.81 1.81 5.89 0.74 5.90 0.90Liver 5.21 1.2 3.34 0.37 3.47 0.4 3.36 0.35 4.42 0.35 4.46 0.27Rt kidney 4.26 1.16 2.83 0.7 3.39 0.83 3.15 0.78 4.69 1.04 4.76 1.14Lt kidney 4.43 1.57 2.39 0.31 2.96 0.42 2.66 0.37 4.84 0.86 4.78 0.92

30

25

20

15

10

5

0

3DCRT6X SMLC6X DMLC

6F DMLC6X RA6F RA

Righ

t eye

Left

eye

Thyr

oid

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rt

Esop

hagu

s

Righ

t lun

g

Live

r

Righ

t kid

ney

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kidn

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lung

V80%

OAR V80%

Figure 3: Graphical plot: 𝑉80% for OARs.

achievable with RA therapy (4.71 Gy (6X RA) and 5.10Gy(6F RA)). Lower values of 𝑉

10% for OARs were possiblewith IMRT compared to RA technique. Average BOT was3.43min (6X DMLC), 1.59min (6F DMLC), 5min (6X RA),and 4.5min (6F RA) compared to 3DCRT (1.262min).

4. Discussions

Dosimetric parameters for PTV were almost similar inall techniques except the minimal target dose (𝐷min). Aminimum dose of 5.76Gy (3DCRT) was the least comparedto others. Thus, CSI with 3DCRT could lead to lesser targetcoverage. IMRT (FF/FFF) and RA therapy (FF/FFF) haveled to eye doses that were within the tolerance limit (RTOG0225).

Hypothyroidism is the most common complicationobserved after RT. Thyroid gland is viewed as a radiation-resistant organ though the range of thyroid-ablative radiation

70605040302010

0

Righ

t eye

Left

eye

Thyr

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3DCRT6X SMLC6X DMLC

6F DMLC6X RA6F RA

V50%

OAR V50%

Figure 4: Graphical plot: 𝑉50% for OARs.

doses seems to be wide, being 10–80Gy according to Fooet al. [9]. Theoretically the development of hypothyroidismin RT patients would primarily depend on 𝑉

30%, the volumereceiving relatively high radiation doses (≥30Gy) thus withthe risk of insufficient post-RT hormone production. Thisvolumemight show considerable interpatient variation, as thesize of the thyroid gland might vary from patient to patient.However, to our knowledge, no study had evaluated theassociation between the thyroid volume exposed to high-doseirradiation and the development of post-RT hypothyroidismin CSI planned with FFF beams.The use of FFF in IMRT andRA for CSI could reduce the risks of hypothyroidism. Also,the late risks such as cardiomyopathy, liver diseases, renalfailure, and esophagitis could be eliminated using FFF beams,due to considerable reduction in doses deposited in OARs.

Acceptable dose to eyes and lesser doses to other criticalorgans were possible with FFF IMRT and FFF RA therapy.3DCRT leads to higher values of 𝐷max and 𝐷mean that couldcause late toxicity (4). 𝑉

80% was similar in all the techniquesfor eyes and other normal structures. The highest 𝑉

80%

ISRN Oncology 5

(26.97% in esophagus) resulted from3DCRT. IMRT (FF/FFF)and RA (FF/FFF) techniques lead to zero percentage of 𝑉

80%which could be more clinically relevant in sparing the OARs.Lesser amount of normal tissues received 50% and 30% dosesin IMRT (FF/FFF) and RA (FF/FFF) compared to 3DCRT.

Treatment delivery efficiency is quantified by lesser BOT.6X DMLC IMRT delivery required more treatment time.3DCRT and 6X SMLC showed no difference in BOT. FFFIMRT/FFF RA had lesser beam on time that improves theefficiency of therapy, by minimizing patient movement andintrafraction variation errors in treatment setup.

5. Conclusion

Using FFF beams in IMRT/RA therapy for CSI had definitedosimetric advantages in target coverage and OAR sparingover flattened photon beam therapy. Lesser BOT achievablewith FFF beams improves efficiency of CSI radiotherapy.In addition, high precision techniques evade the concernover junction doses due to minimal set-up errors. Hence,the use of FFF beams is feasible and effective in treatingmedulloblastoma patients.

Conflict of Interests

The authors declare that there is no conflict of interests.

References

[1] R. J. Packer, A. Gajjar, G. Vezina et al., “Phase III study of cran-iospinal radiation therapy followed by adjuvant chemotherapyfor newly diagnosed average-risk medulloblastoma,” Journal ofClinical Oncology, vol. 24, no. 25, pp. 4202–4208, 2006.

[2] A. Gajjar, R. Hernan,M. Kocak et al., “Clinical, histopathologic,and molecular markers of prognosis: toward a new disease riskstratification system for medulloblastoma,” Journal of ClinicalOncology, vol. 22, no. 6, pp. 984–993, 2004.

[3] T. A. Dolecek, J. M. Propp, N. E. Stroup, and C. Kruchko,“CBTRUS statistical report: primary brain and central nervoussystem tumors diagnosed in the United States in 2005–2009,”Neuro-Oncology, vol. 14, supplement 5, pp. v1–v49, 2012.

[4] G. W. Robinson, Medulloblastoma, American Brain TumorAssociation (ABTA), Chicago, Ill, USA, 2012.

[5] S. D. Sharma, T. Gupta, R. Jalali, Z. Master, R. D. Phurailatpam,and R. Sarin, “High-precision radiotherapy for craniospinalirradiation: evaluation of three-dimensional conformal radio-therapy, intensity-modulated radiation therapy and helicalTomotherapy,”The British Journal of Radiology, vol. 82, no. 984,pp. 1000–1009, 2009.

[6] W. Parker, E. Filion, D. Roberge, and C. R. Freeman, “Intensity-modulated radiotherapy for craniospinal irradiation: targetvolume considerations, dose constraints, and competing risks,”International Journal of Radiation Oncology Biology Physics, vol.69, no. 1, pp. 251–257, 2007.

[7] International Commission on Radiation Units and Measure-ments (ICRU), “Prescribing, recording and reporting photonbeam therapy,” ICRU Report 62, International Commissionon Radiation Units and Measurements (ICRU), Bethesda, Md,USA, 1999, (Supplement to ICRU Report 50): ICRU Publica-tions.

[8] Q. J. Wu, S. Yoo, J. P. Kirkpatrick, D. Thongphiew, and F. F.Yin, “Volumetric Arc intensity-modulated therapy for spinebody radiotherapy: comparisonwith static intensity-modulatedtreatment,” International Journal of Radiation Oncology BiologyPhysics, vol. 75, no. 5, pp. 1596–1604, 2009.

[9] M. L. Foo, E. C. McCullough, R. L. Foote, T. M. Pisansky,and E. G. Shaw, “Doses to radiation sensitive organs andstructures located outside the radiotherapeutic target volumefor four treatment situations,” International Journal of RadiationOncology Biology Physics, vol. 27, no. 2, pp. 403–417, 1993.

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Research Article Use of Flattening Filter-Free …downloads.hindawi.com/archive/2014/769698.pdfResearch Article Use of Flattening Filter-Free Photon Beams in Treating Medulloblastoma: